Insights into the biocontrol and plant growth promotion functions of Bacillus altitudinis strain KRS010 against Verticillium dahliae.

BACKGROUND: Verticillium wilt, caused by the fungus Verticillium dahliae, is a soil-borne vascular fungal disease, which has caused great losses to cotton yield and quality worldwide. The strain KRS010 was isolated from the seed of Verticillium wilt-resistant Gossypium hirsutum cultivar "Zhongzhimian No. 2." RESULTS: The strain KRS010 has a broad-spectrum antifungal activity to various pathogenic fungi as Verticillium dahliae, Botrytis cinerea, Fusarium spp., Colletotrichum spp., and Magnaporthe oryzae, of which the inhibition rate of V. dahliae mycelial growth was 73.97% and 84.39% respectively through confrontation test and volatile organic compounds (VOCs) treatments. The strain was identified as Bacillus altitudinis by phylogenetic analysis based on complete genome sequences, and the strain physio-biochemical characteristics were detected, including growth-promoting ability and active enzymes. Moreover, the control efficiency of KRS010 against Verticillium wilt of cotton was 93.59%. After treatment with KRS010 culture, the biomass of V. dahliae was reduced. The biomass of V. dahliae in the control group (Vd991 alone) was 30.76-folds higher than that in the treatment group (KRS010+Vd991). From a molecular biological aspect, KRS010 could trigger plant immunity by inducing systemic resistance (ISR) activated by salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Its extracellular metabolites and VOCs inhibited the melanin biosynthesis of V. dahliae. In addition, KRS010 had been characterized as the ability to promote plant growth. CONCLUSIONS: This study indicated that B. altitudinis KRS010 is a beneficial microbe with a potential for controlling Verticillium wilt of cotton, as well as promoting plant growth.

An Interview Study of College Students' Health Emergency Literacy in the Context of COVID-19 Normalized Prevention and Control.

Objective: To explore the changes in college students' awareness of health protection under the normalization of COVID-19, and to seek its connection with the epidemic management in colleges and universities, so as to provide reference information for continuous health education activities and the cultivation of college students' health emergency literacy in colleges and universities. Methods: Qualitative interviews were used to understand the extent of health emergency literacy among college students enrolled in the context of a normalized epidemic and the factors associated with it that cause changes around a question outline. Results: The interviewees generally had a lax mentality in the late stage of the interview, the importance they attached to epidemic prevention and control decreased significantly, and the way to know about epidemic protection measures and other knowledge was mainly through the mass news media. All respondents affirm the importance of social software for outbreak prevention and control. All 17 interviewees were able to mention basic outbreak protection methods, but 15 of them showed inconsistent behavior in words and actions later. Conclusion: The vast majority of respondents' health emergency literacy appears to weaken in the late stages of epidemic normalization, and the effect of traditional approaches used by universities to improve college students' health emergency literacy is weak.

Metal-free polychloromethyl radical-initiated cyclization of unactivated N-allylindoles towards pyrrolo[1,2-a]indoles.

A metal-free polychloromethyl radical-initiated cyclization of unactivated alkenes was developed using CH2Cl2 and CHCl3 as the di- and trichloromethyl radical sources. Variously substituted N-allyl-indoles were successfully transformed into the corresponding C2-(di- and trichloromethyl) pyrrolo[1,2-a]indoles in moderate to good yields. This reaction has a broad substrate scope and good functional group tolerance. Dibromomethylated products can also be obtained using CH2Br2 under standard conditions.

LncRNA LEF1-AS1/LEF1/FUT8 Axis Mediates Colorectal Cancer Progression by Regulating α1, 6-Fucosylationvia Wnt/ß-Catenin Pathway.

BACKGROUND: Fucosylation alteration is involved in several steps of human cancer pathogenesis. Dysregulated long non-coding RNA (lncRNA) often leads to malignancy in colorectal cancer (CRC). METHODS: Differential levels of LEF1-AS1, LEF1 and FUT8 are analyzed by qRT-PCR and western blot. Chip, RIP, EMSA and luciferase reporter assay confirm the direct interaction among LEF1-AS1, MLL1, H3K4me3, LEF1 and FUT8. Functionally, CRC cell proliferation, migration and invasion are analyzed by CCK8 assay, colony formation assay, transwell assay and flow cytometry. The xenografts nude mice models, lung metastasis and liver metastasis are established to determine the effect of LEF1-AS1/LEF1/FUT8 axis on CRC progression in vivo. RESULTS: Here, we identify that LEF1-AS1 and LEF1 are higher in CRC tissues than that in adjacent tissues, as well as upregulated in CRC cell lines than that in normal colorectal cells. Altered levels of LEF1-AS1 modulate LEF1 expression, while altered LEF1 could not regulate LEF1-AS1. LEF1-AS1 recruits MLL1 to the promoter region of LEF1, induces H3K4me3 methylation modification and mediates LEF1 transcription. Furthermore, α1-6 fucosyltransferase FUT8 is overexpressed in CRC tissues and positively correlated to LEF1. FUT8 is a direct target of transcription factor LEF1, which regulates FUT8 level. Altered FUT8 also regulates the core fucosylation of CRC cells, and LEF1-AS1 mediates FUT8 level through activation of Wnt/ß-catenin/LEF1 pathway, thereby resulting in ß-catenin nuclear translocation. In addition, LEF1-AS1 mediates the proliferation, migration and invasion of CRC cells in vitro. LEF1-AS1 silence hinders the tumorigenesis, liver and lung metastasis of SW620 cells in vivo, while overexpressed FUT8 abolishes the suppressive impact of LEF1-AS1 repression on the biological behavior of SW620 cells. CONCLUSION: Our studies uncovered a novel mechanism for constitutive LEF1-AS1/LEF1/FUT8 axis in CRC progression by regulating α1, 6-fucosylation via Wnt/ß-catenin pathway, and consequently, as a potential therapeutic target in CRC.

Rhodium-catalyzed C-H activation/cyclization of aryl sulfoximines with iodonium ylides towards polycyclic 1,2-benzothiazines.

The synthesis of 1,2-benzothiazine derivatives through rhodium-catalyzed C-H activation/cyclization of S-aryl sulfoximines with iodonium ylides was developed for the first time. In this report, C-H and N-H bond functionalization was realized towards a series of tricyclic and tetracyclic sulfoximine derivatives with moderate to excellent yields under simple reaction conditions.

RhIII -Catalyzed C6-Selective Oxidative C-H/C-H Crosscoupling of 2-Pyridones with Thiophenes.

A rhodium(III)-catalyzed C6-selective dehydrogenative cross-coupling of 2-pyridones with thiophenes was developed for the synthesis of 6-thiophenyl pyridin-2(1H)-one derivatives. In this reaction, the excellent site selectivity was controlled by the 2-pyridyl directing group on the nitrogen of the pyridone ring. Control experiments indicated that the N-pyridyl was essential for the transformation. To the best of our knowledge, this procedure is the first successful example of the direct C6 heteroarylation of 2-pyridones with electron-rich thiophene derivatives. 4-Pyridone was also used as substrate to generate the corresponding C2 heteroarylated product. Moreover, this pyridyl directing group was readily removable to generate the biheteroaryl structures with a free N-H group.

Rh(iii)-Catalyzed regioselective C4 alkylation of indoles with allylic alcohols: direct access to ß-indolyl ketones.

A Rh(iii)-catalyzed and weak coordination carbonyl guided direct C4 alkylation of indoles with allylic alcohols was developed with excellent regioselectivity. This reaction was conducted under mild conditions, leading to a variety of ß-indolyl ketones with good functional group tolerance in moderate to good yields.

Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway.

BACKGROUND: Exosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells. Human metastases-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA known to promote cell proliferation, metastasis, and invasion in colorectal cancer (CRC). METHODS: The expression of MALAT1 was analyzed in CRC using qRT-PCR. FUT4 and fucosylation levels were detected in CRC clinical samples and CRC cell lines by immunofluorescent staining, western blot and lectin blot analysis. CRC derived exosomes were isolated and used to examine their tumor-promoting effects in vitro and in vivo. RESULTS: The invasive and metastatic abilities of primary CRC cells were enhanced after exposure to exosomes derived from highly metastatic CRC cells, which increased the fucosyltransferase 4 (FUT4) levels and fucosylation not by directly transmitting FUT4 mRNA. Exosomal MALAT1 increased FUT4 expresssion via sponging miR-26a/26b. Furthermore, MALAT1/miR-26a/26b/FUT4 axis played an important role in exosome-mediated CRC progression. Exosomal MALAT1 also mediated FUT4-associated fucosylation and activated the PI3K/AKT/mTOR pathway. CONCLUSIONS: These data indicated that exosomal MALAT1 promoted the malignant behavior of CRC cells by sponging miR-26a/26b via regulating FUT4 and activating PI3K/Akt/mTOR pathway.

Author Correction: Combination of chick embryo and nutrient mixture prevent D-galactose-induced cognitive deficits, immune impairment and oxidative stress in aging rat model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Retraction Note: Functional screen analysis reveals miR-3142 as central regulator in chemoresistance and proliferation through activation of the PTEN-AKT pathway in CML.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A combination of chicken embryo extract and a nutritional supplement protect a rat model of aging against d-galactose-induced dysfunction of mitochondria and autophagy.

The aging process is usually associated with increased oxidative stress and deficiency of tissues and organs, which causes a decline in the life quality of individuals. Some anti-oxidant factors derived from foods have been implicated in delaying senescence and sustaining health. The present study aimed to assess the anti-aging effects and underlying mechanism of the combined application of chicken embryo (CE) extract and a nutritional mixture (NM) of 52 ingredients on the aging process of d-galactose (d-gal)-induced rats. After 90 days of treatment, we observed that CE plus NM administration significantly improved the body weight, visceral indices and histological damage of aging rats. The use of CE or NM alone exhibited similar effects, but was not as effective as the combined use of CE and NM. In addition, the additional nutrients promoted the mitochondrial function of d-galactose-induced rats. With CE + NM supplementation, cells from senescent rats showed decreased accumulation of reactive oxygen species (ROS), increased levels of mitochondrial membrane potential, elevated numbers of mitochondria, and morphological changes towards normalization compared to the un-treated group. Furthermore, autophagosomes and autophagy-related proteins were up-regulated in aging rats upon exposure to CE + NM. Interestingly, we also found that the protein extracts of CE have similar effects to CE. These results indicate the critical role played by CE + NM in promoting the function of mitochondria and autophagy, therefore regulating the aging process in rats. Our study provides a novel compound design of nutritional support to achieve an optimal nutritional status for anti-oxidation and slowing of aging.

Combination of chick embryo and nutrient mixture prevent D-galactose-induced cognitive deficits, immune impairment and oxidative stress in aging rat model.

Aging is spontaneous and inevitable processes that lead to changes in biological systems. The present paper was designed to investigate the anti-aging roles of chick embryo (CE) and nutrient mixture (NM) in aging rats. Aging was induced by administration of D-galactose (D-gal, 500 mg/kg/day for 90 days). CE and NM were administered to aging rats through different dose gavage once a day. Cognitive function assessment was performed using the Morris water maze test. At the end of experiment, serum and tissues were collected for immunity and antioxidation function. The organs and tissues were excised for histological study. The results demonstrated that CE plus NM was superior treatment to improve the histopathologic changes and reverse learning and memory impairment of the aging rats. CE plus NM also increased the spleen and thymus index as well as splenocyte proliferation, and reversed inflammatory cytokine levels. In addition, the biochemical index showed that CE plus NM could improve the antioxidant enzyme activity of the aging rats, decrease lipofuscin (LF) and glutamate content. CE plus NM also inhibited the activation of TLR4/NF-κB pathway stimulated by LPS in splenic B lymphocytes. Overall, these results seem to be implying that CE plus NM was used as potentially natural supplement or functional food for preventing aging.

Correction to: miR-140-5p/miR-149 Affects Chondrocyte Proliferation, Apoptosis, and Autophagy by Targeting FUT1 in Osteoarthritis.

The original version of this article contained mistakes, and the authors would like to correct them.

LncRNA ST3Gal6-AS1/ST3Gal6 axis mediates colorectal cancer progression by regulating α-2,3 sialylation via PI3K/Akt signaling.

Sialylation is associated with cancer progression. Long noncoding RNAs (lncRNAs) have important roles in diverse diseases including cancer. The lncRNA ST3Gal6 antisense 1 (ST3Gal6-AS1) derives from the promoter region of sialyltransferase ST3Gal6. However, the mechanisms by which ST3Gal6-AS1 modulates colorectal cancer (CRC) development through sialylation remain largely unknown. Here, we found that ST3Gal6-AS1 and ST3Gal6 levels were lower in tumor tissues than adjacent normal tissues of CRC patients. The correlation between ST3Gal6-AS1 and ST3Gal6 was further validated in several types of CRC cell lines. In addition, ST3Gal6 was dysregulated and positively correlated to ST3Gal6-AS1. ST3Gal6-AS1 recruited histone methyltransferase MLL1 to the promoter region of ST3Gal6, induced H3K4me3 modification and activated ST3Gal6 transcription. Furthermore, ST3Gal6-AS1/ST3Gal6 axis mediated α-2, 3 sialylation and inhibited the activation of PI3K/Akt signaling, thereby resulting in Foxo1 nuclear translocation in CRC cells. ST3Gal6-AS1 was a target of transcription factor Foxo1 and regulated by Foxo1. ST3Gal6-AS1 also inhibited CRC cell proliferation, metastasis, and promoted cell apoptosis in vitro. Overexpression of ST3Gal6-AS1 significantly decreased the tumorigenesis, lung and liver metastasis of SW620 cells in vivo. ST3Gal6-AS1 expression was negatively correlated with tumor size, lymphatic metastasis, distant metastasis and tumor stage in CRC patients. Collectively, these data indicated that ST3Gal6-AS1, ST3Gal6, PI3K/Akt, and Foxo1 formed a positive feedback loop, which might play a key role in CRC progression.

Long noncoding RNA HOTAIR promotes renal cell carcinoma malignancy through alpha-2, 8-sialyltransferase 4 by sponging microRNA-124.

OBJECTIVES: Accumulating evidence demonstrated that the long noncoding RNA (lncRNA) HOTAIR (Hox transcript antisense intergenic RNA) plays key role in renal cell carcinoma (RCC) malignancy, while microRNA-124 (miR-124) is a tumour suppressor in RCC. The aim of this work was to assess the biological function of HOTAIR and to explore underlying mechanism involved in HOTAIR/miR-124/alpha-2, 8-sialyltransferase 4 (ST8SIA4) axis-regulated progression in RCC. MATERIALS AND METHODS: Real-time PCR analyses and western blots were performed to the levels of HOTAIR, miR-124 and ST8SIA4 expression in human RCC tissues and RCC cell lines (ACHN and 786-O). Bioinformatics analysis and dual-luciferase reporter assay were used to illustrate relationship between HOTAIR and miR-124 in RCC. Colony formation assays, EdU assays, Ki67 assays and apoptosis assays were taken to evaluate cell proliferation. Tumour xenograft was created to explore the functions of HOTAIR and ST8SIA4 in tumorigenesis in vivo. Migration assays, invasion assays and cell adhesion assays and were also taken to analyse the carcinoma progression. RESULTS: In this study, HOTAIR level was confirmed to be significantly upregulated in RCC samples and RCC cell lines compared with those in the paired adjacent tissues and normal renal cell line. Overexpression of HOTAIR promoted the capability of proliferation, migration and invasion in RCC cell lines. HOTAIR directly bound to miR-124, while miR-124 mediated the expression of ST8SIA4 in RCC cell lines. ST8SIA4 was upregulated in RCC tissues and RCC cell lines. Ectopic expression of ST8SIA4 modulated the proliferation, migration and invasion of RCC cells. Further results indicated that HOTAIR promoted the proliferation and metastasis as a competing endogenous RNA to regulate ST8SIA4 expression by sponging miR-124 in RCC. CONCLUSIONS: Our results demonstrated that HOTAIR mediated RCC progression in part through miR-124/ST8SIA4 axis, which functioned as a new prognostic biomarker in RCC.

Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression.

BACKGROUND: Colorectal cancer (CRC) arises in a multistep molecular network process, which is from either discrete genetic perturbation or epigenetic dysregulation. The long non-coding RNAs (lncRNAs), emerging as key molecules in human malignancy, has become one of the hot topics in RNA biology. Aberrant O-glycosylation is a well-described hallmark of many cancers. GALNT7 acts as a glycosyltransferase in protein O-glycosylation, involving in the occurrence and development of CRC. METHODS: The microarrays were used to survey the lncRNA and mRNA expression profiles of primary CRC cell line SW480 and metastatic CRC cell line SW620. Cell proliferation, migration, invasion, and apoptosis were assayed. Xenograft mouse models were used to determine the role of lncRNA-SNHG7 in CRC in vivo. In addition, CNC analysis and competing endogenous analysis were used to detect differential SNHG7 and relational miRNAs expression in CRC cell lines. RESULTS: SNHG7 expression showed a high fold (SW620/SW480) in CRC microarrays. The CRC patients with high expression of SNHG7 had a significantly poor prognosis. Furthermore, SNHG7 promoted CRC cell proliferation, metastasis, mediated cell cycle, and inhibited apoptosis. SNHG7 and GALNT7 were observed for co-expression by CNC analysis, and a negative correlation of SNHG7 and miR-34a were found by competing endogenous RNA (ceRNA) analysis. Further results indicated that SNHG7 facilitated the proliferation and metastasis as a competing endogenous RNA to regulate GALNT7 expression by sponging miR-34a in CRC cell lines. SNHG7 also played the oncogenic role in regulating PI3K/Akt/mTOR pathway by competing endogenous miR-34a and GALNT7. CONCLUSION: The CRC-related SNHG7 and miR-34a might be implicated in CRC progression via GALNT7, suggesting the potential usage of SNHG7/miR-34a/GALNT7 axis in CRC treatment.

LncRNA SNHG7 sponges miR-216b to promote proliferation and liver metastasis of colorectal cancer through upregulating GALNT1.

Accumulating evidence suggests long noncoding RNAs (lncRNAs) play an important role in cancer progression. However, the function of lncRNA SNHG7 in colorectal cancer (CRC) remains unclear. In this study, SNHG7 expression was significantly upregulated in CRC tissues, especially in aggressive cases. In accordance, high level of SNHG7 was observed in CRC cell lines compared to normal colon cells. Furthermore, SNHG7 overexpression promoted the proliferation, migration, and invasion of CRC cell lines, while SNHG7 depletion inhibited invasion and cell viability in vitro. Mechanistically, knockdown of SNHG7 inhibited GALNT1 and EMT markers (E-cadherin and Vimentin). Importantly, SNHG7 directly interacted with miR-216b and downregulation of miR-216b reversed efficiently the suppression of GALNT1 induced by SNHG7 siRNA. Moreover, overexpression of SNHG7 significantly enhanced the tumorigenesis and liver metastasis of SW480 cells in vivo. SNHG7 positively regulated GALNT1 level through sponging miR-216b, and played an oncogenic role in CRC progression. Together, our study elucidated the role of SNHG7 as an miRNA sponge in CRC, and shed new light on lncRNA-directed diagnostics and therapeutics in CRC.

Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/ß-catenin axis.

Osteoarthritis (OA) is a chronic joint disease and hard to cure at present. Accumulating evidence suggests long noncoding RNA-HOTAIR (lncRNA-HOTAIR) plays important role in OA progression. However, the underlying molecular mechanism of HOTAIR in OA progression has not been well elucidated. In the present study, we identified that HOTAIR level was upregulated in OA cartilage tissues. High expression of HOTAIR was correlated with modified Mankin scale, extracellular matrix (ECM) degradation and chondrocytes apoptosis. The expression of miR-17-5p was down-regulated, while alpha-1, 2 fucosyltransferase 2 (FUT2) was increased in OA progression. Luciferase reporter and RNA immunoprecipitation (RIP) assays indicated that HOTAIR could directly bind to miR-17-5p and indirectly upregulate FUT2 level. Functional investigation revealed HOTAIR and FUT2 aggravated ECM degradation and chondrocytes apoptosis, and this effect could be reversed by miR-17-5p. Altered FUT2 modulated the activity of wnt/ß-catenin pathway and HOTAIR/miR-17-5p also mediated wnt/ß-catenin pathway through FUT2. Collectively, our findings indicated that HOTAIR/miR-17-5p/FUT2 axis contributed to OA progression via wnt/ß-catenin pathway, which might provide novel insights into the function of lncRNA-driven in OA.

miR-140-5p/miR-149 Affects Chondrocyte Proliferation, Apoptosis, and Autophagy by Targeting FUT1 in Osteoarthritis.

Osteoarthritis (OA), the most prevalent chronic and degenerative joint disease, is characterized by articular cartilage degradation and chondrocyte injury. Increased cell apoptosis and defective cell autophagy in chondrocytes are a feature of degenerative cartilage. MicroRNAs (miRNAs) have been identified as potential regulators of OA. This study aimed to determine the potential role of miR-140-5p and miR-149 in apoptosis, autophagy, and proliferation in human primary chondrocytes and investigate the underlying mechanism. We revealed the differential expressional profiles of miR-140-5p/149 and fucosyltransferase 1 (FUT1) in the articular cartilage tissues of OA patients and normal people and validated FUT1 was a direct target of miR-140-5p/149. The overexpression of miR-140-5p/149 inhibited apoptosis and promoted proliferation and autophagy of human primary chondrocytes via downregulating FUT1. On the contrary, the downregulation of miR-140-5p/149 inhibited chondrocyte proliferation and autophagy, whereas the effect was reversed by FUT1 knockdown. Taken together, our data suggested that miR-140-5p and miR-149 could mediate the development of OA, which was regulated by FUT1. miR-140-5p/miR-149/FUT1 axis might serve as a predictive biomarker and a potential therapeutic target in OA treatment.